Inflammatory processes and enhanced procoagulant activity are closely related to the development of atherosclerotic plaques. Plaque disruption and subsequent thrombosis are the leading cause of acute coronary syndromes (ACS), including unstable angina, acute myocardial infarction and sudden death. Pro-inflammatory cytokines cause a disruption of normal function of the arterial endothelium leading to the up-regulation of adhesion molecules, which contribute to plaque growth. Circulating levels of pro-inflammatory cytokines are increased in ACS patients and are predictors of the onset and outcome of coronary artery disease (CAD). One of the functions of cytokines is stimulation of tissue factor (TF) expression, which is a potent initiator of the coagulation cascade and plays a major role in plaque thrombogenicity. It has been also suggested that thrombin-driven and contact pathway-independent activation of factor (F) XI can play a role in cardiovascular disease. For example, Minnema et al. (Arterioscler Thromb Vasc Biol 2000; 20(11):2489-2493) reported that 24% of patients with acute myocardial infarction and 8% with unstable angina pectoris had evidence of FXIa presentation in their plasma Minnema's assay was based upon the immunochemical detection of FXIa in complex with C1 inhibitor; one of the numerous serine protease inhibitors present in plasma, suggesting that potentially only a fraction of FXIa present in plasma was detected by this procedure.
The detection of FXIa in plasma is complicated by controversies related to the efficiency of various plasma protease inhibitors towards FXIa. Wuillemin and coworkers suggest that 47% of FXIa added to plasma forms a complex with C1 inhibitor (Wuillemin W A, et al., Blood 1995; 85(6):1517-1526), whereas Scott et al. report that only 8% of FXIa is involved in the complex formation with this inhibitor. (Scott C F, et al., J Clin Invest 1982; 69(4): 844-852)